Lactam-modified polypeptide compounds

Abstract

A class of lactam-modified polypeptide compounds and the use thereof in the preparation of a drug for treating related diseases.

What is claimed is: 
     
         1 . A compound represented by the following formula or a pharmaceutically acceptable salt thereof,
 SEQ ID NO1: YAibEGT FTSDY SIAibLD KK 1 AZ 0 K 0  Z 1 FZ 2 E 0 W LZ 3 AGG PSSGA PPPS 0      SEQ ID NO2: YAibEGT FTSDY SIAibLD KE 0 AQK 0  AFVK 1 W LIAGG PSSGA PPPS 0      SEQ ID NO3: YAibEGT FTSDY SIE 0 LD KK 0 AQK 1  AFVQW LIAGG PSSGA PPPS 0      SEQ ID NO4: YAibEGT FTSDY SIE 0 LD K 0 IAQK 1  AFVQW LIAGG PSSGA PPPS 0      
       wherein 
       Aib has a structure of 
       
         
           
           
               
               
           
         
       
       S 0  is selected from 
       
         
           
           
               
               
           
         
       
       Z 0  is selected from glutamine (Q) and asparagine (N); 
       Z 1  is selected from alanine (A) and glutamic acid (E); 
       Z 2  is selected from valine (V) and isoleucine (I); 
       Z 3  is selected from isoleucine (I) and leucine (L); 
       E 0  and K 0  indicate that the carboxyl group on the side chain of the glutamic acid and the amino group on the side chain of the lysine jointly form a lactam structure, and in this case, K 0 Z 1 FZ 2 E 0  has a structure of 
       
         
           
           
               
               
           
         
       
       E 0 AQK 0  has a structure of 
       
         
           
           
               
               
           
         
       
       E 0 LDKK 0  has a structure of 
       
         
           
           
               
               
           
         
       
       and E 0 LDK 0  has a structure of 
       
         
           
           
               
               
           
         
       
       K 1  indicates that the amino group on the side chain of the lysine is connected to —X—X 1 —X 2 , and has a structure of 
       
         
           
           
               
               
           
         
       
       X is selected from 
       
         
           
           
               
               
           
         
       
       R 1  and R 2  are each independently selected from H and CH 3 ; 
       X 1  is selected from 
       
         
           
           
               
               
           
         
       
       X 2  is selected from 
       
         
           
           
               
               
           
         
       
       m, n and p are each independently selected from 2 and 3; 
       s is selected from 2 and 3; 
       q is selected from 15, 16, 17, 18 and 19. 
     
     
         2 . The compound or the pharmaceutically acceptable salt thereof according to  claim 1 , which is selected from: 
       
         
           
           
               
               
           
         
       
     
     
         3 . The compound or the pharmaceutically acceptable salt thereof according to  claim 1 , wherein X is selected from —C(═O)—CH 2 —. 
     
     
         4 . The compound or the pharmaceutically acceptable salt thereof according to  claim 1 , wherein m, n and p are each independently selected from 2. 
     
     
         5 . The compound or the pharmaceutically acceptable salt thereof according to  claim 1 , wherein s is independently selected from 2. 
     
     
         6 . The compound or the pharmaceutically acceptable salt thereof according to  claim 1 , wherein q is independently selected from 15 and 17. 
     
     
         7 . The compound or the pharmaceutically acceptable salt thereof according to  claim 1 , wherein X 1  is selected from 
       
         
           
           
               
               
           
         
       
     
     
         8 . The compound or the pharmaceutically acceptable salt thereof according to  claim 1 , wherein X 2  is selected from 
       
         
           
           
               
               
           
         
       
     
     
         9 . The compound or the pharmaceutically acceptable salt thereof according to  claim 1 , wherein —X—X 1 —X 2  is selected from 
       
         
           
           
               
               
           
         
       
     
     
         10 . A compound represented by the following formula or a pharmaceutically acceptable salt thereof, selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         11 . A method for treating obesity and diabetes in a subject in need thereof, comprising: administering the compound or the pharmaceutically acceptable salt thereof according to  claim 1  to the subject. 
     
     
         12 . The compound or the pharmaceutically acceptable salt thereof according to  claim 2 , wherein X is selected from —C(O)—CH 2 —. 
     
     
         13 . The compound or the pharmaceutically acceptable salt thereof according to  claim 2 , wherein m, n and p are each independently selected from 2. 
     
     
         14 . The compound or the pharmaceutically acceptable salt thereof according to  claim 2 , wherein s is independently selected from 2. 
     
     
         15 . The compound or the pharmaceutically acceptable salt thereof according to  claim 2 , wherein q is independently selected from 15 and 17. 
     
     
         16 . The compound or the pharmaceutically acceptable salt thereof according to  claim 2 , wherein X 1  is selected from 
       
         
           
           
               
               
           
         
       
     
     
         17 . The compound or the pharmaceutically acceptable salt thereof according to  claim 2 , wherein X 2  is selected from 
       
         
           
           
               
               
           
         
       
     
     
         18 . The compound or the pharmaceutically acceptable salt thereof according to  claim 2 , wherein —X—X 1 —X 2  is selected from 
       
         
           
           
               
               
           
         
       
     
     
         19 . A method for treating obesity and diabetes in a subject in need thereof, comprising: administering the compound or the pharmaceutically acceptable salt thereof according to  claim 10  to the subject.